Hygroscopic, crosslinking coatings and bioadhesives

Abstract

According to the present disclosure, a bioadhesive formulation is provided. The bioadhesive formulation comprises a polycaprolactone dendrimer having a dendrimer core and a plurality of polycaprolactone chains extending from the dendrimer core, wherein at least one of the polycaprolactone chains has an end which is covalently attached with a diazirine, and wherein the diazirine converts to a carbene or a diazoalkyl when a stimulant is applied to the bioadhesive formulation. Methods of forming the bioadhesive formulation are also provided. The bioadhesive could be used in (i) the prevention of thrombosis from tissue fixation and/or (ii) the relief of discomfort and/or pain during and/or after surgery. Preferably, the bioadhesive formulation further comprises a hygroscopic additive, an antithrombotic agent, and/or an anaesthetic agent.

The invention claimed is: 
     
       1. A bioadhesive formulation comprising a polycaprolactone dendrimer having a dendrimer core and a plurality of polycaprolactone chains extending from the dendrimer core, wherein at least one of the polycaprolactone chains has an end which is covalently attached with a diazirine, and wherein the diazirine converts to a carbene and/or a diazoalkyl when a stimulant is applied to the bioadhesive formulation. 
     
     
       2. The bioadhesive formulation according to  claim 1 , wherein each of the polycaprolactone chains comprises one or more repeating units of: 
       
         
           
           
               
               
           
         
         wherein part A of each repeating unit extends away from the dendrimer core and part B of each repeating unit extends toward the dendrimer core, and wherein in the at least one polycaprolactone chain having the end which is covalently attached with the diazirine, part A of the repeating unit arranged furthest away from the dendrimer core forms the end at which the diazirine is covalently attached to the at least one polycaprolactone chain. 
       
     
     
       3. The bioadhesive formulation according to  claim 2 , wherein part A of the repeating unit arranged furthest away from the dendrimer core forms the end at which there is an oxygen for forming an ether linkage, an ester linkage, or an anhydride linkage, with the diazirine. 
     
     
       4. The bioadhesive formulation according to  claim 3 , wherein the diazirine is represented by the formula: 
       
         
           
           
               
               
           
         
         wherein at least one of R 1  to R 5  is hydrogen, —C 1-12  alkyl- which is unsubstituted or substituted with one or more halogens, or —R 6 C(═O)—; 
         wherein the —C 1-12  alkyl- in at least one of R 1  to R 5  is covalently attached to the oxygen to form an ether linkage or an ester linkage with the polycaprolactone chain; 
         wherein the —R 6 C(═O)— in at least one of R 1  to R 5  is covalently attached to the oxygen to form an ester linkage or an anhydride linkage with the polycaprolactone chain; 
         wherein R 6  is a bond or —C 1-12  alkyl- which is unsubstituted or substituted with one or more halogens; and 
         wherein X is hydrogen, halogen or —C 1-12  alkyl substituted with one or more halogens. 
       
     
     
       5. The bioadhesive formulation according to  claim 1 , wherein the diazirine comprises: 
       
         
           
           
               
               
           
         
       
     
     
       6. The bioadhesive formulation according to  claim 1 , wherein the bioadhesive formulation further comprises a hygroscopic additive, an antithrombotic agent, and/or an anaesthetic agent. 
     
     
       7. The bioadhesive formulation according to  claim 6 , wherein the hygroscopic additive comprises anhydrous citric acid, anhydrous ethanol, anhydrous magnesium sulfate, and/or hydroxyapatite. 
     
     
       8. The bioadhesive formulation according to  claim 6 , wherein:
 the antithrombotic agent comprises sebacic acid; or 
 the anaesthetic agent comprises bupivacaine. 
 
     
     
       9. The bioadhesive formulation according to  claim 1 , wherein the bioadhesive formulation is in the form of a liquid formulation, wherein the liquid formulation becomes a cured bioadhesive when the stimulant is applied to the bioadhesive formulation. 
     
     
       10. The bioadhesive formulation according to  claim 1 , wherein the stimulant comprises (i) electromagnetic radiation having one or more wavelengths from 315 nm to 1400 nm, (ii) electromagnetic radiation having one or more intensities in the range of 1 mW·cm −2  to 1000 mW·cm −2 , (iii) a current in the range of 1 mA to 100 mA and/or (iv) a voltage in the range of ±50 V.